Reactions of Diethylazo‐Dicarboxylate with Frustrated Lewis Pairs

Abstract Reactions of PAr3/B(C6F5)3 (Ar=o‐Tol, Mes, Ph) FLPs with diethyl azodicarboxylate (DEAD) afford the corresponding FLP addition products 1–3 in which P−N and B−O linkages are formed. In contrast, the reaction of BPh3, PPh3 and DEAD gave product 4 where P−N and N−B linkages were confirmed. In all cases, other binding modes were computed to be both higher in energy and readily distinguishable by 31P and 11B NMR parameters. These data illustrate the influence of steric demands and electronic structures on the nature of the products of FLP reactions with DEAD.

In all cases, other binding modes were computed to be both higher in energy and readily distinguishable by 31 P and 11 B NMR parameters. These data illustrate the influence of steric demands and electronic structures on the nature of the products of FLP reactions with DEAD.
The discovery in 2006 that combinations of sterically congested Lewis acids and bases could reversibly activate H 2 [1] dislodged the long-held chemical dogma that transition metals alone could react with dihydrogen. This observation was subsequently generalized [2] extending the reactivity of so-called frustrated Lewis pairs (FLPs) to a broad range of main group combinations as well as transition metal reactivity. In addition, the reactivity of FLPs was also extended to a wide variety of small molecules well beyond H 2 . For example, FLPs have been shown to react with CO 2 , CO, SO 2 , N 2 O, [3] olefins, [2b] alkynes, [4] and even CÀ H bonds. [5] This concept has been extended a wide range of main group Lewis acid /base combinations, [6] transition metal [7] and rare earth systems [8] and most recently to group 1 and 2 metal species [9] clearly illustrating the breadth of this new paradigm.
Early applications of this new reactivity concept focused on the development of metal-free hydrogenations [10] and a number of applications in organic synthesis have followed. [11] It is also interesting to see the use of FLPs in a range of disparate areas of interest. For example, the concept has been applied to understand the reactivity of enzymatic activation of H 2, [12] and heterogeneous catalysts. [13] FLPs have also been incorporated into MOFs [14] and exploited as catalysts for polymerization. [15] Another creative application of the concept of FLPs has been reported by the Shaver group. [16] These researchers prepared polymers functionalized with either Lewis acidic 4styryl-diphenylborane or Lewis basic 4-styryl-diphenylphosphine phosphorus fragments. While the combination of these polymers affords FLPs, crosslinking of these polymers was achieved in the presence of diethyl azodicarboxylate (DEAD). The resulting gel materials exhibit the remarkable ability to "self-heal". In studying these systems, Shaver et al. showed that the crosslink is derived from FLP addition to DEAD suggesting new BÀ N and PÀ N bonds were formed (Scheme 1). This finding was consistent with a previous study by Bourissou and coworkers [17] who reported the analogous reaction of the intramolecular FLP C 6 H 4 PiPr 2 (BMes 2 ) with DEAD affording the corresponding adduct C 6 H 4 PiPr 2 (BMes 2 )(NCO 2 Et) 2 (Scheme 1) that contains a six-membered ring derived from the newly formed BÀ N and PÀ N bonds.
Herein, we probe the reactions of DEAD with intermolecular FLPs derived from phosphines and boranes. Experimental and computational data show steric demands and electronic features of the FLP impact the nature of the FLP addition products. In addition, these findings are relevant to the binding mode in previously reported FLP polymers. [16] To the stoichiometric combination of P(o-Tol) 3 /B(C 6 F 5 ) 3 dissolved in CH 2 Cl 2 , DEAD was added and warmed to 40°C for 24 h. After work-up, crystallization afforded compound (o-Tol) 3 PN(CO 2 Et)N=C(OEt)OB(C 6 F 5 ) 3 , 1 in 88 % yield (Scheme 2). The 31 P NMR spectrum showed a resonance at 49.0 ppm while 19 F NMR spectrum gave resonances at À 133.8, À 161.6 and À 166.5 ppm in a ratio of 2 : 1 : 2. The corresponding 11 B resonance gave a signal at À 3.4 ppm. These data are consistent with a phosphorous(V) species and a tetracoordinate boron species. Notably, two sets of 13 C resonances were observed consistent with inequivalent ester groups. Both the 1 H and 13 C NMR spectra of the aryl rings of 1 are inequivalent, consistent with inhibited rotation about the PÀ C bonds, presumably a result of the steric demands of the aryl substituents.
While these data are consistent with the addition of the FLP to DEAD, the precise nature of 1 was confirmed by single crystal XRD ( Figure 1). The structure revealed that the phosphine is added to one of the nitrogen atoms of DEAD, while the borane is bound to the ester carbonyl oxygen atom on the adjacent nitrogen atom. This structure gave rise to new PÀ N and BÀ O distances of 1.684(1) Å and 1.522(2) Å. The NÀ N distance was found to be 1.441 (2) Å while the NÀ C distances were 1.298(2) Å and 1.395(2) Å.
The analogous use of Mes 3 P gave a similar reaction, affording a 31 P signal at 46.1 ppm, a 11 B signal at À 3.5 ppm, and 19 F resonances at À 133.6, À 162.1 and À 168.6 ppm. The similarity of these data to those observed for 1 prompted the formulation of the product 2 as Mes 3 PN(CO 2 Et)N=C(OEt)OB-B(C 6 F 5 ) 3 (Scheme 2). This was confirmed crystallographically ( Figure 2). Like 1, the structure of 2 is directly analogous with PÀ N, NÀ N and OÀ B bond lengths of 1.721(1) Å, 1.445(2) Å, and 1.517(2) Å, respectively. Similarly, the reaction of Ph 3 P/B(C 6 F 5 ) 3 with DEAD afforded closely related spectral data and thus the formulation of the product 3 as Ph 3 PN(CO 2 Et)N=C(OEt)OB(C 6 F 5 ) 3 (Scheme 2). It was isolated in 75 % yield and exhibited similar spectroscopic parameters with 31 P and 11 B chemical shifts at 45.6 and À 3.1 ppm, respectively.
It is noteworthy that the structure of 1-3 stands in contrast to the DEAD addition products with C 6 H 4 PR 2 (BMes 2 ) and Mes 2 PAr/BPh 3 previously reported by the groups of Bourissou and Shaver, respectively. In the former case the chelating nature of the intramolecular FLP affords a six-membered ring via the new BÀ N/PÀ N bonds to the nitrogen atoms of DEAD, thus presumably enhancing stability of this mode of binding. Bourissou also described the analogous reaction of the intramolecular FLP with PhNCO, where both experimental structures and theoretical calculations supported the notion that steric congestion leads to the thermodynamic favoring of BÀ O binding.
In the case of the intermolecular polymeric FLP described by Shaver et al., the BÀ N and PÀ N binding was proposed based on the observation of broad 31 P and 11 B NMR resonances at 44.3 ppm and 6.4 ppm, respectively. The breadth of the signals was interpreted as evidence of a dynamic exchange process. To probe the possibility of dynamic behavior in the present compounds, variable temperature NMR spectra for compound 1 Scheme 2. Synthesis of 1-4.

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Research Article doi.org /10.1002/chem.202201701 were recorded in CDCl 3 over the temperatures from 25-65°C. While both the 31 P and 11 B signals sharpened at elevated temperatures, no significant signal shift was observed. Interestingly, dissolution of 1 in d 8 -toluene shows two 31 P NMR signals at 49.0 and 51.8 ppm, while the 11 B NMR signals are observed at À 2.4 and À 3.7 ppm. The impact of solvent was also examined for the initial mixture of P(o-Tol) 3 , B(C 6 F 5 ) 3 and DEAD. In CDCl 3 solution, the single 31 P resonance attributable to 1 was observed. In contrast, in toluene the reaction mixture showed four 31 P NMR signals at 49.0, 50.2, 51.1 and 53.3 ppm in an intensity ratio of 13 : 9 : 27 : 1 (Figure 3). Efforts to monitor this mixture over time were challenged by the precipitation of 1 from solution.
To address these observations, DFT computations for the potential isomers of 1 in CH 2 Cl 2 solution were performed at the PW6B95-D3/def2-QZVP + COSMO-RS//TPSS-D3/def2-TZVP + COSMO level of theory. [18] Initial structures generated according to conceivable Lewis structures were checked with the CREST method using the xTB program for low-lying conformers as input. [19] In addition to DFT-computed Gibbs energies (at 298 K and 1 M concentration) used in our discussion, the corresponding 31 P, 11 B and 13 C NMR chemical shifts were computed at the GIAO TPSS-D3/def2-QZVP level using TPSS-D3/def2-TZVP + COSMO optimized geometries (Figure 3, top). The addition of P(o-Tol) 3 to DEAD is À 11.3 kcal/mol exergonic over a low barrier of 13.3 kcal/mol (via TSA) to form the PÀ N adduct Aa (see Supporting Information). Further barrierless addition of B(C 6 F 5 ) 3 to Aa is À 22.2, À 19.6, À 19.2, and À 9.3 kcal/mol exergonic to form the isomers I, II, IIa, and III of 1 (Figure 3, top), with a new BÀ O for the former three and a new BÀ N bond for III. The lowest energy isomer I was consistent with the crystallographic data, with the new BÀ O bond being cis to the C=N double bond. Taking the experimentally observed 31 P and 11 B for this structure as reliable reference, the DFT-computed NMR parameters provided useful structural probe for closely related isomers. It is noteworthy that both isomers II, IIa with the new BÀ O bond being trans to the C=N double bond show different cis/trans orientation about the amide-like CÀ N bond of the free ester carbonyl group (without borane-binding), which are almost degenerate in free energy but with distinguishable 31 P NMR signals as observed in experiment; such isomers are about 3 kcal/mol less favored thermodynamically than isomer I, but still involve the same PÀ N/BÀ O linkages. The isomer III involving the BÀ N/PÀ N binding mode is significantly less stable than I by more than 10 kcal/mol and exhibits different 31 P and 11 B chemical shifts at 54.9 and À 5.8 ppm, respectively. These data affirm that the PÀ N/BÀ O binding mode is thermodynamically favored and readily distinguishable spectroscopically from other isomers. It is interesting to note that the DFT-computed spectral data fit well with the observations made in solution affording clear assignment of the four 31 P resonances seen in the initial mixture in toluene to the corresponding isomers, further affirming the preference for the PÀ N/BÀ O binding mode.
To probe the impact of the electrophilicity of the borane, the corresponding reaction of the less Lewis acidic BPh 3 , PPh 3 and DEAD was also monitored spectroscopically. The 31 P NMR signal was seen at 52.1 ppm, while the 11 B NMR resonance appeared at 2.0 ppm. This product 4 was isolated in 78 % yield (Scheme 2) and crystallization from toluene affording X-ray quality crystals. The structure ( Figure 4) revealed FLP capture of DEAD via the BÀ N/NÀ P binding mode with BÀ N and PÀ N bond distances of 1.653(5) Å and 1.693(3) Å.
Our DFT calculations show that the addition of less bulky PPh 3 to DEAD is À 16.6 kcal/mol exergonic to form the more Figure 3. DFT-computed Gibbs free energy path (at 298 K and 1 M concentration in CH 2 Cl 2 (or toluene in parentheses), relative to initial FLP and DEAD reactants) and NMR shifts for potential isomers of 1 (top). Experimental 31 P NMR spectrum for P(o-Tol) 3 , B(C 6 F 5 ) 3 and DEAD in toluene at 40°C, 24 h (bottom).

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Research Article doi.org /10.1002/chem.202201701 stable PÀ N adduct Ac (see Supporting Information). Interestingly, in contrast to the previous cases, further addition of less Lewis acidic BPh 3 to Ac is now À 0.3, À 5.7 and À 7.0 kcal/mol exergonic to form the similar isomers I, II and III of 4 but with a completely reversed energetic order. The observed 31 P and 11 B signals at 52.1 and 2.0 ppm for the lowest energy isomer III with the BÀ N/PÀ N binding mode agree very well with the respective computed values of 52.0 ppm and 0.2 ppm, and it is 1.3 kcal/mol more stable than the BÀ O/PÀ N bound isomer II.
Probing the previously reported reaction of BPh 2 (C 6 H 4 CH=CH 2 )/PMes 2 (C 6 H 4 CH=CH 2 ) and DEAD [16] demonstrates that steric effects alter the outcome of the reaction. In CH 2 Cl 2 solution, addition of bulky phosphine PMes 2 Ph to DEAD is À 5.0 kcal/mol exergonic to form the PÀ N adduct Ad (see Supporting Information); while further addition of BPh 2 (C 6 H 4 CH=CH 2 ) to Ad is À 5.3 and À 4.7 kcal/mol exergonic affording the BÀ O/PÀ N isomers I and II but 9.4 kcal/mol endergonic to form the BÀ N/PÀ N bound isomer III of 5. In less polar toluene solution, the formation of adduct Ad is still À 1.1 kcal/mol exergonic while the addition of BPh 2 (C 6 H 4 CH=CH 2 ) remains À 8.8 and À 9.0 kcal/mol exergonic yielding the isomers I and II but is 6.3 kcal/mol endergonic in the formation of the isomer III. The BÀ N/PÀ N isomer III of the product 5 is thus thermodynamically unfavorable. Furthermore, the experimental 31 P and 11 B NMR parameters (44.3, 6.4 ppm) agree very well with 5.4 ppm) for the isomer II, but are quite distinct from those observed for 1 (49.0, À 3.4 ppm) and 4 (52.1, 2.0 ppm). These findings suggest that the product of the reaction of BPh 3 /PMes 2 Ph and DEAD is almost certainly the type II BÀ O/PÀ N isomers.
In conclusion, we have examined the interactions of a series of intermolecular FLPs with DEAD. These data confirm the previously unknown binding mode in which PÀ N and OÀ B linkages are formed. DFT computations show that this is the lowest free energy isomer for reactions with B(C 6 F 5 ) 3 . In contrast, for reactions with the less Lewis acidic BPh 3 the steric demand of the phosphine influences the nature of the product. The use of PPh 3 favors the BÀ N/PÀ N products, while bulky PMes 3 affords the BÀ O/NÀ P product. These binding modes are readily distinguished by both experimental and computational 31 P and 11 B NMR parameters. Collectively these data clarify the nature of the binding mode of FLPs with DEAD and provide a rare example [20] of the influence of steric demands and electronics on the nature of the products from the FLP capture of a substrate. We are continuing to examine the utility of FLP systems in the capture and reactivity of small molecules.
Supplementary data including synthetic and spectral data, DFT-computed energies and optimized Cartesian coordinates are deposited.
Deposition Number(s) 2168932 (for 1), 2168933 (for 2), 2172267 (for 4) contain(s) the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.